Fixed reference edge system for slide loading and unloading

ABSTRACT

A fixed reference edge system that guides a glass slide from a slot of a slide rack onto a scanning stage and guides the glass slide from the scanning stage into the slot of the slide rack. In an embodiment, the fixed reference edge has a first side that is parallel to a side of the slot of the slide rack. The system comprises an assembly that includes a push bar configured to push the slide from the slot onto the scanning stage, and a pull bar configured to pull the slide from the scanning stage into the slot of the slide rack. When the slide is pulled into the slide rack, the long edge of the slide is pressed against the first side of the fixed reference edge to maintain a parallel orientation between the slide and the slot of the slide rack.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/624,042, filed on Dec. 18, 2019, which is a national stage entry ofInternational Patent App. No. PCT/US2018/063465, filed on Nov. 30, 2018,which claims priority to U.S. Provisional Patent App. No. 62/593,448,filed on Dec. 1, 2017, which are all hereby incorporated herein byreference as if set forth in full.

BACKGROUND Field of the Invention

The present invention relates generally to a digital slide scanningapparatus (e.g., for pathology) and, more particularly, to a fixedreference edge that is positioned to guide a glass slide being loadedfrom a slide rack onto a scanning stage or being unloaded from thescanning stage into the slide rack.

Related Art

Digital pathology is an image-based information environment which isenabled by computer technology that allows for the management ofinformation generated from a physical slide. Digital pathology isenabled in part by virtual microscopy, which is the practice of scanninga specimen on a physical glass slide and creating a digital slide imagethat can be stored, viewed, managed, and analyzed on a computer monitor.With the capability of imaging an entire glass slide, the field ofdigital pathology has exploded and is currently regarded as one of themost promising avenues of diagnostic medicine in order to achieve evenbetter, faster, and cheaper diagnosis, prognosis, and prediction ofimportant diseases, such as cancer.

Glass slides that are processed by a digital slide scanning apparatusare very fragile and highly valuable. Unfortunately, conventionaldigital slide scanners tend to damage glass slides when the glass slidesare conveyed from a slide rack onto the scanning stage or conveyed fromthe scanning stage into the slide rack. Therefore, what is needed is asystem and method that overcomes these significant problems found in theconventional systems described above.

SUMMARY

Accordingly, a fixed reference edge system is described herein thatguides a glass slide being loaded from a slide rack onto the scanningstage and also guides the glass slide being unloaded from the scanningstage back into the slide rack. The system includes a fixed referenceedge that has a first side that is parallel to a side of the slot of theslide rack from which the slide was unloaded. The system also includes apush/pull assembly that includes a push bar that is configured to pushthe glass slide out of the slot of the slide rack directly onto thescanning stage such that a long edge of the glass slide is adjacent thefirst side of the fixed reference edge. The push/pull assembly alsoincludes a pull bar that is configured to pull the glass slide from thescanning stage into the slot of the slide rack. When the glass slide ispulled into the slot of the slide rack, the long edge of the glass slideis pressed against the first side of the fixed reference edge toposition the long edge of the glass slide parallel to the side of theslot of the slide rack for insertion into the slot of the slide rackwithout damaging the glass slide.

In an embodiment, a digital slide scanning apparatus is disclosed thatcomprises: a stage comprising a recessed slot within which a glass sliderests during scanning, and a reference edge positioned to form a longedge of the recessed slot; and an assembly configured to push a glassslide out of a slide rack directly into the recessed slot on the stage,and pull a glass slide from the recessed slot on the stage directly intothe slide rack, wherein the reference edge prevents yaw rotation of aglass slide as the glass slide is pulled into the slide rack by theassembly. The reference edge may extend along an entire long edge of aglass slide when the glass slide is positioned in the recessed slot onthe stage.

In an embodiment, the recessed slot comprises a through hole configuredto allow illumination of the glass slide from below during scanning. Therecessed slot may comprise at least two support surfaces on opposingsides of the through hole, wherein the at least two support surfaces areconfigured to support at least two opposing edges of a glass slide whenthe glass slide is positioned in the recessed slot on the stage. Thereference edge may be positioned on a portion of one of the at least twosupport surfaces.

In an embodiment, the stage further comprises one or more finger groovesconfigured to expose one or more portions of opposing short edges of aglass slide when the glass slide is positioned in the recessed slot onthe stage. The assembly may comprise a pull bar and a push bar, whereinthe pull bar is configured to pull a glass slide from the recessed sloton the stage directly into the slide rack, and wherein the push bar isconfigured to push a glass slide out of a slide rack directly into therecessed slot on the stage. The pull bar may comprise at least one pullfinger configured to engage a short edge of a glass slide, via the oneor more finger grooves, when the glass slide is positioned in therecessed slot on the stage, and pull the glass slide from the recessedslot on the stage directly into the slide rack by sliding within the oneor more finger grooves. The at least one pull finger may be configuredto lower down to engage the short edge of a glass slide, and raise up todisengage the short edge of a glass slide. For example, the at least onepull finger may be configured to lower down and raise up by rotatingaround a longitudinal axis of the pull bar, wherein the digital slidescanning apparatus further comprises at least one processor configuredto control the rotation of the pull finger. The push bar may comprise atleast one push finger configured to engage a short edge of a glass slidewhen the glass slide is in the slide rack, and push the glass slide fromthe slide rack directly into the recessed slot on the stage. In anembodiment, the assembly further comprises an opening between the pushbar and the pull bar, wherein the opening is configured to allow theslide rack to pass through.

The digital slide scanning apparatus may further comprise at least oneprocessor configured to control at least one motor to move the assemblyin two directions along a linear axis that is parallel with alongitudinal axis of the recessed slot on the stage and a longitudinalaxis of a slot in the slide rack. The stage may further comprise aspring arm configured to press a long edge of a glass slide towards thereference edge so as to prevent the yaw rotation of the glass slide. Thedigital slide scanning apparatus may further comprise at least oneprocessor that, while a glass slide is pulled from the stage into theslide rack, controls the spring arm to press the long edge of the glassslide towards the reference edge to prevent the yaw rotation of theglass slide.

In an embodiment, a method is disclosed that comprises: controlling amotor to drive an assembly to push a first glass slide from a slot of aslide rack directly onto a scanning stage of a digital slide scanningapparatus, so as to position a long edge of the glass slide adjacent toa side of a reference edge on the scanning stage, wherein the side ofthe reference edge is parallel to a side of the slot of the slide rack;controlling the digital slide scanning apparatus to scan the glassslide; and, subsequent to scanning the glass slide, controlling themotor to drive the assembly to pull the glass slide from the scanningstage into the slot of the slide rack, wherein the side of the referenceedge prevents yaw rotation of the glass slide while the glass slide ispulled into the slot of the slide rack. The method may further comprise,while the glass slide is pulled into the slot of the slide rack,controlling a spring arm on the scanning stage to press the long edge ofthe glass slide towards the side of the reference edge to prevent theyaw rotation of the glass slide.

Other features and advantages of the present invention will become morereadily apparent to those of ordinary skill in the art after reviewingthe following detailed description and accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The structure and operation of the present invention will be understoodfrom a review of the following detailed description and the accompanyingdrawings in which like reference numerals refer to like parts and inwhich:

FIG. 1A is a perspective-view diagram illustrating an example push/pullassembly of a digital slide scanning apparatus, according to anembodiment;

FIG. 1B is a perspective-view diagram illustrating an example push/pullassembly, slide rack, and scanning stage of a digital slide scanningapparatus, according to an embodiment;

FIG. 2A is a perspective-view diagram illustrating an example scanningstage with reference edge and glass slide, according to an embodiment;

FIG. 2B is a perspective-view diagram illustrating an example scanningstage with reference edge and glass slide, according to an embodiment;

FIG. 3A is a block diagram illustrating an example processor-enableddevice that may be used in connection with various embodiments describedherein;

FIG. 3B is a block diagram illustrating an example line scan camerahaving a single linear array, according to an embodiment;

FIG. 3C is a block diagram illustrating an example line scan camerahaving three linear arrays, according to an embodiment; and

FIG. 3D is a block diagram illustrating an example line scan camerahaving a plurality of linear arrays, according to an embodiment.

DETAILED DESCRIPTION

Certain embodiments disclosed herein provide for a fixed reference edgeto facilitate slide loading from a slide rack onto a scanning stage andslide unloading from the scanning stage into a slot of the slide rack.After reading this description it will become apparent to one skilled inthe art how to implement the invention in various alternativeembodiments and alternative applications. However, although variousembodiments of the present invention will be described herein, it isunderstood that these embodiments are presented by way of example only,and not limitation. As such, this detailed description of variousalternative embodiments should not be construed to limit the scope orbreadth of the present invention as set forth in the appended claims.

1. Example Push/Pull Assembly

FIG. 1A is a perspective-view diagram illustrating an example push/pullassembly 100 of a digital slide scanning apparatus, according to anembodiment. In the illustrated embodiment, the push/pull assembly 100includes a pull bar 110 comprising one or more pull fingers 112extending from a surface of the pull bar 110. The push/pull assembly 100also includes a push bar 120 comprising one or more push fingers 122extending from a surface of the push bar 120. In the illustratedembodiment, there are two pull fingers 112 and two push fingers 122.However, in alternative embodiments, there may be fewer pull fingers 112and/or push fingers 122 (e.g., one) or more pull fingers 112 and/or pushfingers 122 (e.g., three, four, five, etc.). In addition, the number ofpull fingers 112 may be the same as the number of push fingers 122 ordifferent (e.g., fewer or more) than the number of push fingers 122.

In an embodiment, the pull fingers 112 are configured to raise up tobring the fingers 112 out of contact with an edge of a glass slide 585,and to lower down to bring the fingers 112 into contact with the edge ofthe glass slide 585. For example, the pull fingers 112 may rotate up anddown within a rotational range around the longitudinal axis of the pullbar 110. In contrast, the push fingers 122 may be positionally fixed.

In an embodiment, the one or more pull fingers 112 and the one or morepush fingers 122 are positioned along the same linear axis X-X andspaced apart by an opening 130 between the ends of the pull fingers 112and the ends of the push fingers 122. The width of the opening 130,orthogonal to the linear axis X-X, may be at least as wide as the shortedge of a glass slide 585, and the length of the opening 130, along thelinear axis X-X, may be at least as long as the long edge of the glassslide 585. In an embodiment, the push/pull assembly 100 is substantiallyin the shape of a letter “C” with a slide rack opening 130 that isconfigured to allow at least a portion of a slide rack 300, as well asslides 585 within the slide rack 300, to be positioned between the pullfingers 112 and the push 122 fingers, with the pull fingers 112 and thepush fingers 122 oriented within the width of the short edge of a glassslide 585 stored in the slide rack 300.

FIG. 1B is a perspective-view diagram illustrating an example push/pullassembly 100, in combination with a scanning stage 200 and a slide rack300, in operation within a digital slide scanning apparatus, accordingto an embodiment. In the illustrated operation, the push bar 120 of thepush/pull assembly 100 is extended into the slide rack 300. Thepush/pull assembly 100 may either be loading a glass slide 585 from aslot of the slide rack 300 onto the scanning stage 200 or unloading theglass slide 585 from the scanning stage 200 into the slot in the sliderack 300.

2. Example Scanning Stage

The scanning stage 200 comprises a through hole 240 to allowillumination during scanning. The through hole has support surfacesalong its perimeter that define a slot into which a glass slide 585 isinserted and by which the glass slide 585 is supported above the throughhole. In an embodiment, the scanning stage 200 also comprises areference edge 210 that is positioned on one of the support surfaces,such that a first side of the reference edge 210 is parallel to a sideof the slot in the slide rack 200 into which the glass slide 585 isinserted. A spring arm 220 is attached to a top surface of the scanningstage 200 and configured to press the glass slide 585 against the firstside of the reference edge 210, in order to maintain a parallelorientation between the long edge of the glass slide 585, that ispressed against the first side of the reference edge 210, and the sideof the slot in the slide rack into which the glass slide 585 isinserted. Advantageously, this prevents yaw rotation (i.e., rotationaround an axis orthogonal to the plane of the scanning stage 200), atleast when unloading the glass slide 585 from the scanning stage 200into the slide rack 300.

FIG. 2A is a perspective-view diagram illustrating an example scanningstage 200 with a reference edge 210 and a glass slide 585, according toan embodiment. In the illustrated embodiment, the scanning stage 200comprises a reference edge 210 positioned with a first side that isadjacent a long edge of the glass slide 585 positioned on the scanningstage 200 for scanning. The scanning stage 200 also comprises a springarm 220 configured to press the glass slide 585 against the first sideof the reference edge 210. As illustrated, in an embodiment, there is nocontact between the spring arm 220 and the glass slide 585 when theglass slide 585 is being loaded onto the scanning stage 200. Forexample, as the glass slide 585 is being loaded onto the scanning stage200, a processor 555 of the digital slide scanning apparatus may controlthe spring arm 220 to move away from the edge 222 of the slot into whichthe glass slide 585 is inserted so as to avoid contacting the glassslide 585 or at least avoid applying pressure to the glass slide 585.

In an embodiment, the scanning stage 200 comprises one or more fingergrooves 202 formed as recesses into the top surface of the scanningstage 200 and extending into the recessed slot into which the glassslide 585 is inserted for scanning. The finger grooves 202 may logicallyextend along an entire longitudinal length of the slot of the scanningstage 200 into which the slide 585 is inserted, but may be separatedinto two sections 202A and 202B by the through hole 240 in the scanningstage 200. The finger grooves 202 are configured to receive both thepull fingers 112 and the push fingers 122 for unloading and loading. Forexample, the pull fingers 112 of the pull bar 110 of the push/pullassembly 100 may lower down into the finger grooves 202A to engage afirst short edge of the glass slide 585, positioned on the scanningstage 200, and slide along the finger grooves 202 so that the push/pullassembly 100 can pull the glass slide 585 fully off of the scanningstage 200 and into the slide rack 300. In addition, the push fingers 122may engage a second short edge, opposite the first short edge, of aglass slide 585, within the slide rack 300, to push the glass slide 585onto the scanning stage 200 when the slide 585 is being loaded onto thescanning stage 200. While pushing the glass slide 585 onto the scanningstage 200, the push fingers 122 may slide into the finger grooves 202Bof the scanning stage 200 to fully push the slide 585 into the insertionslot of the scanning stage 200.

In an embodiment, the edges 212 and 222 defining the recessed slot, intowhich the glass slide 585 is inserted, may be beveled to facilitate morereliable loading of the glass slide 585 from the slide rack 300 onto thescanning stage 200. For example, in the illustrated embodiment, therecessed slot, into which the glass slide 585 is loaded onto thescanning stage 200, has at least three sides. One of the three sides isformed by the reference edge 210. Advantageously, all three sides of therecessed slot may be beveled, including the edges formed by the scanningstage 200 and the edge formed by the reference edge 210. Alternatively,all three sides may be unbeveled or only some of the three sides may bebeveled.

FIG. 2B is a perspective-view diagram illustrating an example scanningstage 200 with a reference edge 210 and a glass slide 585, according toan embodiment. In the illustrated embodiment, as the glass slide 585 isbeing unloaded from the scanning stage 200 into the slide rack 300, thespring arm 220 applies positive pressure to the long edge of the glassslide 585. For example, as the glass slide 585 is being unloaded fromthe scanning stage 200, a processor 555 of the digital slide scanningapparatus may control the spring arm 220 to move toward the edge 222 ofthe slot into which the glass slide 585 is inserted, so as to contactand apply pressure to the glass slide 585. The pressure, applied by thespring arm 220 to one long edge of the glass slide 585, also presses theother long edge of the glass slide 585 against the reference edge 210,so as to prevent yaw rotation.

In the illustrated embodiment, the scanning stage 200 also includes athrough hole 240, configured to allow the glass slide 585 to beilluminated from below during scanning. There are one or more supportsurfaces along a perimeter of the through hole 240. The support surfacesare parallel to a top surface of the scanning stage 200, but recessedbelow the top surface of the scanning stage 200 to form a recessedinsertion slot for slides 585. In an embodiment, the depth of therecessed slot may be less than the thickness of a conventional glassslide 585. In an embodiment, the spring arm 220 is similarly recessedbelow the top surface of the scanning stage 200 to allow the spring arm220 to contact an edge of the glass slide 585.

3. Example Embodiments

In an embodiment, a digital slide scanning apparatus includes a stageupon which a glass slide is positioned for scanning, the stagecomprising a reference edge positioned adjacent the long edge of theglass slide when the glass slide is positioned on the stage forscanning. The digital slide scanning device also includes a push/pullassembly configured to push a slide out of a slide rack directly ontothe stage, the push/pull assembly further configured to pull a slidefrom the stage directly back into the slide rack, where the referenceedge prevents yaw rotation of the glass slide as the slide is pulledback into the slide rack.

In an embodiment, the reference edge extends along the entire long edgeof the glass slide when the glass slide is positioned on the stage forscanning. The stage may also include a through hole configured to allowillumination of the glass slide during scanning, the through hole havingat least two support surfaces parallel to a surface of the scanningstage, the at least two support surfaces configured to support at leasttwo edges of the glass slide when the glass slide is positioned on thestage for scanning. In an embodiment, the reference edge is positionedon one of the at least two support surfaces of the through hole.

In an embodiment, the stage further comprises one or more finger groovesconfigured to allow access to a short edge of the glass slide when theglass slide is positioned on the stage for scanning.

In an embodiment, the push/pull assembly stage comprises a push bar anda pull bar, the push bar configured to push a slide out of a slide rackdirectly onto the stage for scanning and the pull bar configured to pulla glass slide from the stage directly back into the slide rack. In anembodiment, the push bar comprises at least one push finger configuredto engage a short edge of the glass slide and push the glass slide fromthe slide rack directly onto the scanning stage. In an embodiment, thepull bar comprises at least one pull finger configured to engage theglass slide and pull the glass slide from the stage directly back intothe slide rack. In an embodiment, the pull bar comprises at least onepull finger configured to extend into the one or more finger grooves toengage the glass slide and pull the glass slide from the stage directlyback into the slide rack. In an embodiment, the push/pull assemblyfurther comprises a slide rack opening between the push bar and the pullbar, the slide rack opening configured to allow a slide rack to passthrough.

In an embodiment, a method of safely loading and unloading slides from aslide rack includes using a motor to drive a push/pull assembly to pusha first glass slide from a first slot of a slide rack directly onto ascanning stage of a digital slide scanning device, wherein a long edgeof the first glass slide is positioned on the scanning stage adjacent afirst side of a reference edge, wherein the first side is parallel to aside of the first slot of the slide rack. The method also includes usingthe digital slide scanning device to scan the first glass slide andsubsequent to scanning the first glass slide, using the motor to drivethe push/pull assembly to pull the first glass slide from the scanningstage into the first slot of the slide rack, wherein the first side ofthe reference edge prevents yaw rotation of the first glass slide whilethe first glass slide is pulled into the first slot. In an embodiment,the method also includes pressing the long edge of the first glass slideagainst the first side of the reference edge to prevent yaw rotation ofthe first glass slide while the first glass slide is pulled into thefirst slot.

4. Example Digital Slide Scanning Apparatus

FIG. 3A is a block diagram illustrating an example processor-enableddevice 550 that may be used in connection with various embodimentsdescribed herein. Alternative forms of the device 550 may also be usedas will be understood by the skilled artisan. In the illustratedembodiment, the device 550 is presented as a digital imaging device(also referred to as a digital slide scanning apparatus, digital slidescanner, scanner, scanner system, digital imaging device, etc.) thatcomprises one or more processors 555, one or more memories 565, one ormore motion controllers 570, one or more interface systems 575, one ormore movable stages 580 that each support one or more glass slides 585with one or more samples 590, one or more illumination systems 595 thatilluminate the sample, one or more objective lenses 600 that each definean optical path 605 that travels along an optical axis, one or moreobjective lens positioners 630, one or more optional epi-illuminationsystems 635 (e.g., included in a fluorescence scanner system), one ormore focusing optics 610, one or more line scan cameras 615 and/or oneor more area scan cameras 620, each of which define a separate field ofview 625 on the sample 590 and/or glass slide 585. The various elementsof the scanner system 550 are communicatively coupled via one or morecommunication busses 560. Although there may be one or more of each ofthe various elements of the scanner system 550, for simplicity in thedescription, these elements will be described in the singular exceptwhen needed to be described in the plural to convey the appropriateinformation.

The one or more processors 555 may include, for example, a centralprocessing unit (CPU) and a separate graphics processing unit (GPU)capable of processing instructions in parallel, or the one or moreprocessors 555 may include a multi-core processor capable of processinginstructions in parallel. Additional separate processors may also beprovided to control particular components or perform particularfunctions such as image processing. For example, additional processorsmay include an auxiliary processor to manage data input, an auxiliaryprocessor to perform floating point mathematical operations, aspecial-purpose processor having an architecture suitable for fastexecution of signal processing algorithms (e.g., digital-signalprocessor), a slave processor subordinate to the main processor (e.g.,back-end processor), an additional processor for controlling the linescan camera 615, the stage 580, the objective lens 225, and/or a display(not shown). Such additional processors may be separate discreteprocessors or may be integrated with the processor 555. The one or moreprocessors 555 may be configured to control the motor that drives thepush/pull assembly 100, and further configured to control movement ofthe scanning stage 200 and the slide rack 300, to thereby control theoverall workflow of the digital imaging device and the loading of glassslides 585 from the slide rack 300 onto the stage 200 and the unloadingof glass slides 585 from the stage 200 into the slide rack 300.

The memory 565 provides storage of data and instructions for programsthat can be executed by the processor 555. The memory 565 may includeone or more volatile and/or non-volatile computer-readable storagemediums that store the data and instructions, including, for example, arandom access memory, a read only memory, a hard disk drive, a removablestorage drive, and/or the like. The processor 555 is configured toexecute instructions that are stored in memory 565 and communicate viacommunication bus 560 with the various elements of the scanner system550 to carry out the overall function of the scanner system 550.

The one or more communication busses 560 may include a communication bus560 that is configured to convey analog electrical signals and mayinclude a communication bus 560 that is configured to convey digitaldata. Accordingly, communications from the processor 555, the motioncontroller 570, and/or the interface system 575 via the one or morecommunication busses 560 may include both electrical signals and digitaldata. The processor 555, the motion controller 570, and/or the interfacesystem 575 may also be configured to communicate with one or more of thevarious elements of the scanning system 550 via a wireless communicationlink.

The motion control system 570 is configured to precisely control andcoordinate X-Y-Z movement of the stage 580 and the objective lens 600(e.g., via the objective lens positioner 630). The motion control system570 is also configured to control movement of any other moving part inthe scanner system 550. For example, in a fluorescence scannerembodiment, the motion control system 570 is configured to coordinatemovement of optical filters and the like in the epi-illumination system635.

The interface system 575 allows the scanner system 550 to interface withother systems and human operators. For example, the interface system 575may include a user interface to provide information directly to anoperator and/or to allow direct input from an operator. The interfacesystem 575 is also configured to facilitate communication and datatransfer between the scanning system 550 and one or more externaldevices that are directly connected (e.g., a printer, removable storagemedium, etc.) or external devices, such as an image server system, anoperator station, a user station, and an administrative server system,that are connected to the scanner system 550 via a network (not shown).

The illumination system 595 is configured to illuminate a portion of thesample 590. The illumination system 595 may include, for example, alight source and illumination optics. The light source could be avariable intensity halogen light source with a concave reflective mirrorto maximize light output and a KG-1 filter to suppress heat. The lightsource could also be any type of arc-lamp, laser, or other source oflight. In an embodiment, the illumination system 595 illuminates thesample 590 in transmission mode such that the line scan camera 615and/or area scan camera 620 sense optical energy that is transmittedthrough the sample 590. Alternatively or additionally, the illuminationsystem 595 may be configured to illuminate the sample 590 in reflectionmode such that the line scan camera 615 and/or area scan camera 620sense optical energy that is reflected from the sample 590. Overall, theillumination system 595 is configured to be suitable for interrogationof the microscopic sample 590 in any known mode of optical microscopy.

In an embodiment, the scanner system 550 optionally includes anepi-illumination system 635 to optimize the scanner system 550 forfluorescence scanning. Fluorescence scanning is the scanning of samples590 that include fluorescence molecules, which are photon sensitivemolecules that can absorb light at a specific wavelength (excitation).These photon sensitive molecules also emit light at a higher wavelength(emission). Because the efficiency of this photoluminescence phenomenonis very low, the amount of emitted light is often very low. This lowamount of emitted light typically frustrates conventional techniques forscanning and digitizing the sample 590 (e.g., transmission modemicroscopy). Advantageously, in an optional fluorescence scanner systemembodiment of the scanner system 550, use of a line scan camera 615 thatincludes multiple linear sensor arrays (e.g., a time delay integration(TDI) line scan camera) increases the sensitivity to light of the linescan camera by exposing the same area of the sample 590 to each of themultiple linear sensor arrays of the line scan camera 615. This isparticularly useful when scanning faint fluorescence samples with lowemitted light.

Accordingly, in a fluorescence scanner system embodiment, the line scancamera 615 is preferably a monochrome TDI line scan camera.Advantageously, monochrome images are ideal in fluorescence microscopybecause they provide a more accurate representation of the actualsignals from the various channels present on the sample. As will beunderstood by those skilled in the art, a fluorescence sample 590 can belabeled with multiple florescence dyes that emit light at differentwavelengths, which are also referred to as “channels.”

Furthermore, because the low and high end signal levels of variousfluorescence samples present a wide spectrum of wavelengths for the linescan camera 615 to sense, it is desirable for the low and high endsignal levels that the line scan camera 615 can sense to be similarlywide. Accordingly, in a fluorescence scanner embodiment, a line scancamera 615 used in the fluorescence scanning system 550 is a monochrome10-bit 64-linear-array TDI line scan camera. It should be noted that avariety of bit depths for the line scan camera 615 can be employed foruse with a fluorescence scanner embodiment of the scanning system 550.

The movable stage 580 is configured for precise X-Y axes movement undercontrol of the processor 555 or the motion controller 570. The movablestage may also be configured for movement in a Z axis under control ofthe processor 555 or the motion controller 570. The moveable stage isconfigured to position the sample in a desired location during imagedata capture by the line scan camera 615 and/or the area scan camera.The moveable stage is also configured to accelerate the sample 590 in ascanning direction to a substantially constant velocity and thenmaintain the substantially constant velocity during image data captureby the line scan camera 615. In an embodiment, the scanner system 550may employ a high-precision and tightly coordinated X-Y grid to aid inthe location of the sample 590 on the movable stage 580. In anembodiment, the movable stage 580 is a linear motor based X-Y stage withhigh precision encoders employed on both the X and the Y axes. Forexample, very precise nanometer encoders can be used on the axis in thescanning direction and on the axis that is in the directionperpendicular to the scanning direction and on the same plane as thescanning direction. The stage is also configured to support the glassslide 585 upon which the sample 590 is disposed.

The sample 590 can be anything that may be interrogated by opticalmicroscopy. For example, a glass microscope slide 585 is frequently usedas a viewing substrate for specimens that include tissues and cells,chromosomes, DNA, protein, blood, bone marrow, urine, bacteria, beads,biopsy materials, or any other type of biological material or substancethat is either dead or alive, stained or unstained, labeled orunlabeled. The sample 590 may also be an array of any type of DNA orDNA-related material such as cDNA, RNA, or protein that is deposited onany type of slide or other substrate, including any and all samplescommonly known as microarrays. The sample 590 may be a microtiter plate,for example a 96-well plate. Other examples of the sample 590 includeintegrated circuit boards, electrophoresis records, petri dishes, film,semiconductor materials, forensic materials, and machined parts.

Objective lens 600 is mounted on the objective positioner 630 which, inan embodiment, may employ a very precise linear motor to move theobjective lens 600 along the optical axis defined by the objective lens600. For example, the linear motor of the objective lens positioner 630may include a 50 nanometer encoder. The relative positions of the stage580 and the objective lens 600 in X-Y-Z axes are coordinated andcontrolled in a closed loop manner using motion controller 570 under thecontrol of the processor 555 that employs memory 565 for storinginformation and instructions, including the computer-executableprogrammed steps for overall operation of the scanning system 550.

In an embodiment, the objective lens 600 is a plan apochromatic (“APO”)infinity-corrected objective with a numerical aperture corresponding tothe highest spatial resolution desirable, where the objective lens 600is suitable for transmission mode illumination microscopy, reflectionmode illumination microscopy, and/or epi-illumination mode fluorescencemicroscopy (e.g., an Olympus 40×, 0.75 NA or 20×, 0.75 NA).Advantageously, objective lens 600 is capable of correcting forchromatic and spherical aberrations. Because objective lens 600 isinfinity corrected, focusing optics 610 can be placed in the opticalpath 605 above the objective lens 600 where the light beam passingthrough the objective lens becomes a collimated light beam. The focusingoptics 610 focus the optical signal captured by the objective lens 600onto the light-responsive elements of the line scan camera 615 and/orthe area scan camera 620 and may include optical components such asfilters, magnification changer lenses, and/or the like. The objectivelens 600 combined with focusing optics 610 provides the totalmagnification for the scanning system 550. In an embodiment, thefocusing optics 610 may contain a tube lens and an optional 2×magnification changer. Advantageously, the 2× magnification changerallows a native 20X objective lens 600 to scan the sample 590 at 40×magnification.

The line scan camera 615 comprises at least one linear array of pictureelements (“pixels”). The line scan camera may be monochrome or color.Color line scan cameras typically have at least three linear arrays,while monochrome line scan cameras may have a single linear array orplural linear arrays. Any type of singular or plural linear array,whether packaged as part of a camera or custom-integrated into animaging electronic module, can also be used. For example, a3-linear-array (“red-green-blue” or “RGB”) color line scan camera or a96-linear-array monochrome TDI may also be used. TDI line scan camerastypically provide a substantially better signal-to-noise ratio (SNR) inthe output signal by summing intensity data from previously imagedregions of a specimen, yielding an increase in the SNR that is inproportion to the square-root of the number of integration stages. TDIline scan cameras comprise multiple linear arrays. For example, TDI linescan cameras are available with 24, 32, 48, 64, 96, or even more lineararrays. The scanner system 550 also supports linear arrays that aremanufactured in a variety of formats including some with 512 pixels,some with 1,024 pixels, and others having as many as 4,096 pixels.Similarly, linear arrays with a variety of pixel sizes can also be usedin the scanner system 550. The salient requirement for the selection ofany type of line scan camera 615 is that the motion of the stage 580 canbe synchronized with the line rate of the line scan camera 615, so thatthe stage 580 can be in motion with respect to the line scan camera 615during the digital image capture of the sample 590.

The image data generated by the line scan camera 615 is stored in aportion of the memory 565 and processed by the processor 555 to generatea contiguous digital image of at least a portion of the sample 590. Thecontiguous digital image can be further processed by the processor 555,and the processed contiguous digital image can also be stored in thememory 565.

In an embodiment with two or more line scan cameras 615, at least one ofthe line scan cameras 615 can be configured to function as a focusingsensor that operates in combination with at least one of the line scancameras 615 that is configured to function as an imaging sensor. Thefocusing sensor can be logically positioned on the same optical axis asthe imaging sensor, or the focusing sensor may be logically positionedbefore or after the imaging sensor with respect to the scanningdirection of the scanner system 550. In an embodiment with at least oneline scan camera 615 functioning as a focusing sensor, the image datagenerated by the focusing sensor is stored in a portion of the memory565 and processed by the one or more processors 555 to generate focusinformation to allow the scanner system 550 to adjust the relativedistance between the sample 590 and the objective lens 600 to maintainfocus on the sample during scanning. Additionally, in an embodiment, theat least one line scan camera 615 functioning as a focusing sensor maybe oriented such that each of a plurality of individual pixels of thefocusing sensor is positioned at a different logical height along theoptical path 605.

In operation, the various components of the scanner system 550 and theprogrammed modules stored in memory 565 enable automatic scanning anddigitizing of the sample 590, which is disposed on a glass slide 585.The glass slide 585 is securely placed on the movable stage 580 of thescanner system 550 for scanning the sample 590. Under control of theprocessor 555, the movable stage 580 accelerates the sample 590 to asubstantially constant velocity for sensing by the line scan camera 615,where the speed of the stage is synchronized with the line rate of theline scan camera 615. After scanning a stripe of image data, the movablestage 580 decelerates and brings the sample 590 to a substantiallycomplete stop. The movable stage 580 then moves orthogonal to thescanning direction to position the sample 590 for scanning of asubsequent stripe of image data (e.g., an adjacent stripe). Additionalstripes are subsequently scanned until an entire portion of the sample590 or the entire sample 590 is scanned.

For example, during digital scanning of the sample 590, a contiguousdigital image of the sample 590 is acquired as a plurality of contiguousfields of view that are combined together to form an image stripe. Aplurality of adjacent image stripes are similarly combined together toform a contiguous digital image of a portion of the sample 590 or theentire sample 590. The scanning of the sample 590 may include acquiringvertical image stripes or horizontal image stripes. The scanning of thesample 590 may be either top-to-bottom, bottom-to-top, or both(bi-directional) and may start at any point on the sample.Alternatively, the scanning of the sample 590 may be eitherleft-to-right, right-to-left, or both (bi-directional) and may start atany point on the sample. Additionally, it is not necessary that imagestripes be acquired in an adjacent or contiguous manner. Furthermore,the resulting image of the sample 590 may be an image of the entiresample 590 or only a portion of the sample 590.

In an embodiment, computer-executable instructions (e.g., programmedmodules or other software) are stored in the memory 565 and, whenexecuted, enable the scanning system 550 to perform the variousfunctions described herein. In this description, the term“computer-readable storage medium” is used to refer to any media used tostore and provide computer executable instructions to the scanningsystem 550 for execution by the processor 555. Examples of these mediainclude memory 565 and any removable or external storage medium (notshown) communicatively coupled with the scanning system 550 eitherdirectly or indirectly (e.g., via a network).

FIG. 3B illustrates a line scan camera having a single linear array 640,which may be implemented as a charge coupled device (“CCD”) array. Thesingle linear array 640 comprises a plurality of individual pixels 645.In the illustrated embodiment, the single linear array 640 has 4,096pixels. In alternative embodiments, linear array 640 may have more orfewer pixels. For example, common formats of linear arrays include 512,1,024, and 4,096 pixels. The pixels 645 are arranged in a linear fashionto define a field of view 625 for the linear array 640. The size of thefield of view varies in accordance with the magnification of the scannersystem 550.

FIG. 3C illustrates a line scan camera having three linear arrays, eachof which may be implemented as a CCD array. The three linear arrayscombine to form a color array 650. In an embodiment, each individuallinear array in the color array 650 detects a different color intensity(e.g., red, green, or blue). The color image data from each individuallinear array in the color array 650 is combined to form a single fieldof view 625 of color image data.

FIG. 3D illustrates a line scan camera having a plurality of lineararrays, each of which may be implemented as a CCD array. The pluralityof linear arrays combine to form a TDI array 655. Advantageously, a TDIline scan camera may provide a substantially better SNR in its outputsignal by summing intensity data from previously imaged regions of aspecimen, yielding an increase in the SNR that is in proportion to thesquare root of the number of linear arrays (also referred to asintegration stages). A TDI line scan camera may comprise a largervariety of numbers of linear arrays. For example, common formats of TDIline scan cameras include 24, 32, 48, 64, 96, 120 and even more lineararrays.

The above description of the disclosed embodiments is provided to enableany person skilled in the art to make or use the invention. Variousmodifications to these embodiments will be readily apparent to thoseskilled in the art, and the generic principles described herein can beapplied to other embodiments without departing from the spirit or scopeof the invention. Thus, it is to be understood that the description anddrawings presented herein represent a presently preferred embodiment ofthe invention and are therefore representative of the subject matterwhich is broadly contemplated by the present invention. It is furtherunderstood that the scope of the present invention fully encompassesother embodiments that may become obvious to those skilled in the artand that the scope of the present invention is accordingly not limited.

What is claimed is:
 1. A digital slide scanning apparatus comprising: astage comprising a recessed slot within which a glass slide rests duringscanning, a reference edge positioned to form one edge of the recessedslot, and a spring arm configured to press one edge of the glass slidetowards the reference edge; a push/pull assembly configured to push theglass slide out of a slide rack into the recessed slot on the stage, andpull the glass slide from the recessed slot on the stage into the sliderack; and at least one hardware processor configured to, while the glassslide is pulled from the recessed slot on the stage into the slide rack,control the spring arm to press the one edge of the glass slide towardsthe reference edge.
 2. The digital slide scanning apparatus of claim 1,wherein the reference edge extends along an entire length of the oneedge of the glass slide when the glass slide is positioned in therecessed slot on the stage.
 3. The digital slide scanning apparatus ofclaim 1, wherein the recessed slot comprises a through hole configuredto allow illumination of the glass slide from below during scanning. 4.The digital slide scanning apparatus of claim 3, wherein the recessedslot comprises at least two support surfaces on opposing sides of thethrough hole, and wherein the at least two support surfaces areconfigured to support at least two opposing edges of the glass slidewhen the glass slide is positioned in the recessed slot on the stage. 5.The digital slide scanning apparatus of claim 4, wherein the referenceedge is positioned on a portion of one of the at least two supportsurfaces.
 6. The digital slide scanning apparatus of claim 1, whereinthe stage further comprises one or more finger grooves configured toexpose one or more portions of opposing short edges of the glass slidewhen the glass slide is positioned in the recessed slot on the stage. 7.The digital slide scanning apparatus of claim 6, wherein the push/pullassembly comprises a push bar and a pull bar, wherein the push bar isconfigured to push the glass slide out of a slide rack into the recessedslot on the stage, and wherein the pull bar is configured to pull theglass slide from the recessed slot on the stage into the slide rack. 8.The digital slide scanning apparatus of claim 7, wherein the pull barcomprises at least one pull finger configured to engage a short edge ofthe glass slide, via the one or more finger grooves, when the glassslide is positioned in the recessed slot on the stage, and pull theglass slide from the recessed slot on the stage into the slide rack bysliding within the one or more finger grooves.
 9. The digital slidescanning apparatus of claim 8, wherein the at least one pull finger isconfigured to lower down to engage the short edge of the glass slide,and raise up to disengage the short edge of the glass slide.
 10. Thedigital slide scanning apparatus of claim 9, wherein the at least onepull finger is configured to lower down and raise up by rotating aroundan axis of the pull bar, and wherein the at least one processor isfurther configured to control the rotation of the pull finger.
 11. Thedigital slide scanning apparatus of claim 10, wherein the axis is thelongitudinal axis of the pull bar.
 12. The digital slide scanningapparatus of claim 7, wherein the push bar comprises at least one pushfinger configured to engage a short edge of the glass slide when theglass slide is in the slide rack, and push the glass slide from theslide rack into the recessed slot on the stage.
 13. The digital slidescanning apparatus of claim 12, wherein the at least one push finger ispositionally fixed.
 14. The digital slide scanning apparatus of claim 7,wherein the push/pull assembly further comprises an opening between thepush bar and the pull bar, and wherein the opening is configured toallow the slide rack to pass through.
 15. The digital slide scanningapparatus of claim 14, wherein the push bar comprises at least one pushfinger, wherein the pull bar comprises at least one pull finger, andwherein the opening is between the at least one push finger and the atleast one pull finger.
 16. The digital slide scanning apparatus of claim15, wherein both the at least one push finger and the at least one pullfinger are positioned along a linear axis of the opening.
 17. Thedigital slide scanning apparatus of claim 1, wherein the push/pullassembly forms a C shape.
 18. The digital slide scanning apparatus ofclaim 1, wherein the at least one processor is configured to control atleast one motor to move the push/pull assembly in two directions along alinear axis that is parallel with a longitudinal axis of the recessedslot on the stage and a longitudinal axis of a slot in the slide rack.19. A method comprising: driving a push/pull assembly to push a glassslide from a slot of a slide rack onto a scanning stage of a digitalslide scanning apparatus, so as to position one edge of the glass slideadjacent to a side of a reference edge on the scanning stage, whereinthe side of the reference edge is parallel to a side of the slot of theslide rack; scanning the glass slide; subsequent to scanning the glassslide, driving the push/pull assembly to pull the glass slide from thescanning stage into the slot of the slide rack; and, while the glassslide is pulled into the slot of the slide rack, pressing the one edgeof the glass slide towards the side of the reference edge.
 20. Themethod of claim 19, further comprising, while the glass slide is beingpushed from the slot of the slide rack, controlling a spring arm on thescanning stage to move away from the glass slide so as to avoidcontacting the glass slide.